Clinical Trials in Medical Retina
AREDS (Age- Related Eye Disease Study)
Diabetic Retinopathy Study (DRS)
Early Treatment Diabetic Retinopathy Study (ETDRS)
Diabetes Control and Complications Trial (DCCT)
United Kingdom Prospective Diabetes Study (UKPDS)
The goal was to determine the efficacy of intravitreous aflibercept injections compared to sham in preventing potentially vision-threatening complications in eyes with moderate to severe NPDR. The role of anti-VEGF in managing NPDR without center-involved diabetic macular edema (CI-DME) has not been established.
Clinical trial, eyes with moderate to severe NPDR without CI-DME were randomized to receive 2.0 mg aflibercept or sham. Treatment was given at baseline; 1, 2, and 4 months; and every 4 months through 2 years. Between 2 and 4 years, treatment was deferred if the eye had mild NPDR or better. Aflibercept was administered in both groups if CI-DME with vision loss (≥10 letters at 1 visit or 5-9 letters at 2 consecutive visits) or high-risk proliferative diabetic retinopathy (PDR) developed.
Main outcomes measures
Development of CI-DME with vision loss or PDR.
From 2016 to 2020, 328 participants (399 eyes) with moderate to severe NPDR without CI-DME were randomized to aflibercept injections (n = 200) or sham (n = 199). The 2-year cumulative probability of developing CI-DME with vision loss or PDR was 16.3% with aflibercept vs. 43.5% with sham. The 2-year cumulative probability of developing PDR was 13.5% in the aflibercept group vs. 33.2% in the sham, and the 2-year cumulative probability of developing CI-DME with vision loss was 4.1% in the aflibercept group vs. 14.8% in the sham group. The mean (SD) change in VA from baseline to 2 years was not significant, -0.9 (5.8) letters with aflibercept and -2.0 (6.1) letters with sham.
20% loss of follow-up.
Eyes with moderate to severe NPDR treatment with periodic aflibercept decreased the development of PDR or vision-reducing CI-DME. However, through 2 years, preventive aflibercept did not confer VA benefit compared with observation plus treatment with aflibercept only after development of PDR or vision-reducing CI-DME.
Pearls for clinical practice
Eyes with moderate to severe NPDR can be observed and treated if required.
- Maturi RK, Glassman AR, Josic K, et al. Effect of Intravitreous Anti-Vascular Endothelial Growth Factor vs Sham Treatment for Prevention of Vision-Threatening Complications of Diabetic Retinopathy: The Protocol W Randomized Clinical Trial. JAMA Ophthalmol. 2021;139(7):701-712. doi:10.1001/jamaophthalmol.2021.0606